Intermediate precision validation: how many instruments?

[labcat]

In my company we have some HPLC instruments, all the same brand and model.
Usually, when I perform validations studies I include two different HPLC systems as possible source of variation (together with analyst, day, column, etc).
I have always assumed that when you have proved that results do not change between the two instruments, you can extend the assumption to all other HPLC systems, at least if you don't change the instrument model.

Recently, an external auditor seemed to disagree with this point of view, requiring a confirm that release analyses were performed on the same instrument where the validation was performed.
Now I am curious: is this point a common opinion?
Because it seems to me quite unpractical either to include all the HPLC systems of the laboratory in a validation study, or "to lock" the possibility to perform an analysis only on those two instruments where the validation was performed.
Thank you for opinion

[Robotjock]

Labcat,
I would content that your assumption is correct. In addition, the method system suitability testing should provide assurance the (different) HPLC system is performing appropriately.

To require product release using the instrument that the method was validated on would be very difficult once you have replaced that instrument (and/or associated modules)!!!

[tom jupille]

Robotjock is dead-on. Ask your auditor what part of "If you meet system suitability requirements, then the system is suitable for the analysis." is unclear. (But ask in a nice way! )

[Consumer Products Guy]

We target two HPLC systems and columns of three different lots. We do not differentiate between DAD detector for UV and VWD detectors. Last year we did a validation using conductivity detector; we did buy a second conductivity detector as a backup, and for the validation. But if we were to do a validation using HPLC-MS, we only have one system, so that would have to do.
By the way, we have GC capillary columns that do not have serial numbers or lot numbers on their tags, and I was wondering if cGMP would rather have three capillary columns for this type of validation testing as well???

[Dan]

Wow! Can't bad ideas like this just die a slow death instead of being perpetuated?

At two pharma companies (actually just particular divisions/departments within those companies) that I worked for, the policy was to have the method validation (or at least a good part of it) performed on an HPLC system in order for that system to be used to generate GMP valid data with that method.

The policy was still in place when I left one of those companies as they just love to do extra work for no reason other than "that's the way we have always done it". At the other company, they came to their senses and the QA group was convinced to drop this absurd policy.

As you can tell, I have strong feelings against this; I don't like extra work that has no value added other than someone's idea of job security. The FDA doesn't require this, so why do it?

You prove the robustness of the method using multiple systems, column lots, analysts, etc. as the other posters (and the ICH) have noted.

Each HPLC undergoes an IQ/OQ/PQ to be used for GMP work. Then, as robotjock noted, you have the system suitability to ensure that the HPLC is performing properly for that analysis run.

Now, all that said, there is one small caveat. Depending on the type of method, the validation may have included a determination of the LOD/LOQ. The limit of detection/quantitation can change from instrument to instrument, day to day, etc. Thus, the USP is considering adding a 'detection sensitivity' requirement for the system suitability criteria. The USP has delayed the implementation of this new requirement in General Chapter <621> pending further review as older monograph methods may have difficulty meeting the requirement. You can read about that at the USP website:
http://www.usp.org/USPNF/notices/postpo ... er621.html

The recommendation from the USP is for the system suitability for new methods to include a detection sensitivity when the method is used for imuprity analysis. The reason is that there has been a push for this requirement. I think that it may already be in the EP (sorry I don't have a copy to confirm) and that the ICH PDG has it under consideration.

Just my two cents.
Regards,
Dan

[syk.insight]

For release testing, it is not necessary to involve only those intruments that were used for the validation.Valid Instruments using similar hardware and software are acceptable as long as they meet system suitability requiremnts.Your auditor seems to be some inexperienced person in the field.

[labcat]

thanks a lot for your opinions